Francesco William Guglielmi

Altered status of antioxidant vitamins and fatty acids in patients with inactive inflammatory bowel disease

BACKGROUND & AIMS Data regarding the nutritional status, antioxidant compounds and plasma fatty acid (FA) composition in inactive IBD are conflicting. We compared plasma levels of antioxidants and FA of patients with inactive IBD with active IBD and controls. METHODS Plasma levels of vitamin C, vitamin E, carotenoids, saturated, monounsaturated and polyunsaturated FA, inflammatory markers and nutritional status were determined after an overnight fast in 132 patients with quiescent IBD (40.6+/-13.2 years, 87F/45M), 35 patients with active disease (37.9+/-12.1 years, 25F/10M) and 45 age- and BMI-matched healthy controls (38.1+/-10.5 years, 39F/6M). Results are expressed as mean+/-SD or median [25th percentile;75th percentile]. RESULTS Body mass index (BMI) was normal in inactive (23.9+/-4.7 kg/m(2)), active IBD (22.7+/-4.2 kg/m(2)) and controls (22.3+/-1.9 kg/m(2)). Compared with controls patients with quiescent IBD showed significantly decreased plasma levels of carotenoids (1.85 [1.37;2.56] vs 1.39 [0.88;1.87] micromol/L) and vitamin C (62.3 [48.7;75.0] vs 51.0 [36.4;77.6] micromol/L), increased levels of saturated FA (3879 [3380;4420] vs 3410 [3142;3989] micromol/L) and monounsaturated FA (2578 [2258;3089] vs 2044 [1836;2434] micromol/L) and similar levels of vitamin E and polyunsaturated FA. Results in active disease were similar to inactive disease. CONCLUSION This study shows that antioxidant status and FA profile in a larger population of IBD patients are disturbed independently from disease activity and despite normal overall nutritional status.

Estradiol and Testosterone Levels in Patients Undergoing Partial Hepatectomy A.Possible Signal for Hepatic Regeneration

In five adult male patients undergoing a 40–60% partial hepatectomy, serum sex hormone levels before and after hepatic resection were determined. Blood was drawn immediately prior to each surgical procedure and at specified time points postoperatively. Compared to hormone levels found prior to surgery, following major hepatic resection, estradiol levels increase at 24 and 48 hr, while testosterone levels decline, being significantly reduced at 96 and 144 hr. These data demonstrate that adult males who undergo a 40–60% partial hepatectomy experience alterations in their sex hormone levels similar to those observed in male rats following a 70% hepatectomy. These changes in sex hormone levels have been associated in animals with an alteration of the sex hormone receptor status of the liver that is thought to participate in the initiation of the regenerative response. These studies suggest, but do not prove, that in man, as in the case of the rat, sex hormones may participate in the initiation of or at least modulate in part the regenerative response that occurs following a major hepatic resection.

Depletion of mitochondrial DNA in the skeletal muscle of two cirrhotic patients with severe asthenia.

Qualitative and quantitative alterations of mitochondrial DNA (mtDNA) in the skeletal muscle from two patients with cirrhosis and severe asthenia have been studied. The 4977 bp (mtDNA(4977)) and the 7436 bp (mtDNA(7436)) mtDNA deletions, as well as other mtDNA deletions, revealed by long extension PCR (LX-PCR), were found in the two patients, whereas the 10,422 bp (mtDNA(10,422)) mtDNA deletion was absent. Altogether, the qualitative alterations of mtDNA in cirrhotic patients with severe asthenia were comparable to those of age-matched healthy individuals. The mtDNA content, on the contrary, was substantially decreased in both patients with respect to control. Such mtDNA depletion might be explained by an increased, disease-related, oxidative damage to mtDNA, which probably affects the replication of the mitochondrial genome as already suggested in other oxidative stress-associated diseases.

MtDNA Deletions in Aging and in Nonmitochondrial Pathologies

To establish a reliable set of reference data for use as the healthy age-matched counterpart of potential or assessed pathologic cases with mitochondrial involvement, we performed a wide search for mtDNA deletions (mtDNA4977, mtDNA7436, mtDNA10422, and others) in the skeletal muscle in five age-classes of healthy individuals (135 subjects). A similar search was carried out in different nonmitochondrial pathologic situations such as oculopharyngeal muscular dystrophy (OPMD) and cirrhosis with severe asthenia (AC). A summary of the results in FIGURE 1 indicates that healthy individuals have an age-related increase in the number of mtDNA deleted species and in the average level of mtDNA4977 (FIG. 1, bottom line). Comparison with a healthy age-matched class shows in both OPMD cases a higher number of deleted species and a higher level of mtDNA4977 than in the counterpart.2,3 This strongly suggests that even in nonmitochondrial pathologies of nuclear origin such as OPMD, in which no defect of the mitochondrial respiratory chain is detected, mitochondrial suffering may be present, causing an increase in mtDNA deletions. Conversely, comparison with age-matched healthy classes of the four AC cases shows similar numbers of mtDNA deletions and lower levels of mtDNA4977 in patients as in their counterparts, suggesting that asthenia is probably related to a loss of muscle fibers rich in mitochondria, as also suggested by a reduction in the mtDNA/nuclearDNA ratio found in the same specimens

Effect of Ranitidine on Acetaminophen-Induced Hepatotoxicity in Dogs

The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramus-cular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose-response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals.

Catheter-related complications in long-term home parenteral nutrition patients with chronic intestinal failure.

Background Home Parenteral Nutrition is a therapeutic option to improve quality of life in chronic intestinal failure. Aims To describe frequency of complications both in cancer and non-cancer patients. Methods This study was performed on 270 adult patients (52% with cancer, 48% without cancer) followed for a total of 371 years of treatment. Mean duration of therapy was 191±181 for cancer and 830±1168 days/patient for non-cancer. The treatment was administered by a competent, dedicated provider. Patients received our prescribed “all-in-one admixtures” at their homes. Results Catheter-related complications/1000-days-catheter was 1.40; mechanical complications were comparable in cancer (0.82) and non-cancer (0.91) patients while a statistically significant difference was observed between cancer (0.71) and non-cancer (0.46) patients for sepsis. Bacterial infections were more frequent in non-cancer, mycotic infections primarily affected cancer patients. In our experience 49% of the patients were readmitted, with a low incidence rate of 0.89/1000 days-catheter. The incidence of hepatobiliary complications in our population was 65%. The degree of liver damage was related to short bowel syndrome and to length of treatment. Conclusions This study indicated that cancer patients are more vulnerable to CVC-related infections during Home Parenteral Nutrition and that a safer Home Parenteral Nutrition protocol should be adopted in order to contain CVC-related complications.

Psychomotor dysfunctions in alcoholic and post-necrotic cirrhotic patients without overt encephalopathy.

ABSTRACT— Psychometric tests, visual reaction time tests and electroencephalograms were performed in 26 cirrhotic patients without overt portal‐systemic encephalopathy and in 26 healthy individuals. Cirrhotics performed poorly, compared with controls, on intelligence, learning and memory, perceptual motor and spatial tests. Non‐alcoholic scored lower than alcoholic cirrhotics compared with controls in most tests. Visual reaction time ability was lower in cirrhotics than controls, but the etiology of the cirrhosis did not influence the test results. EEG was normal in all subjects. We conclude that psychomotor tests are the most useful fool for the detection of latent encephalopathy and in the discrimination of different cirrhosis.

Circadian rhythm of hepatic cytosolic and nuclear estrogen receptors

The distribution of estrogen receptor between the cytosolic and nuclear compartments were evaluated in liver of male rats to determine whether a circadian rhythm exists. Cytosolic receptor reached a maximum level at 400 hours and a minimum at 2000 and 2400 hr. Nuclear receptor reached a maximum level at 800 hr and was lowest at 1600 and 2000 hr. Serum estradiol levels were also highest at 800 hr and lowest at 1600 hr. The variations in cytosolic and nuclear receptors are not reciprocal; in fact, the overall content of receptor in the liver is not constant and also displays a circadian rhythm.

Undernutrition, risk of malnutrition and obesity in gastroenterological patients: A multicenter study

AIM To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last three-six months. Values of Malnutrition Universal Screening Tool (MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment (MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition (OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.

Introduction to the Minisymposium on mucosal healing in inflammatory bowel disease

Mucosa healing (MH) currently represents the primary endpoint o verify the efficacy of any pharmacological treatment in inflamatory bowel disease (IBD). In fact, many studies have highlighted hat gastroenterologists’ attitude towards MH changed drastically hen anti-TNF therapy was introduced, and determined a rapid nd unexpected improvement in clinical symptoms and endoscopic esions. Persistence of mucosal inflammation, even in the absence f symptoms, is a recognized risk factor for disease relapse and ecurrence and has recently been associated with increased risk f colorectal cancer (1–5) in ulcerative colitis (UC). It has also been roven that MH strongly correlates with the reduction of: (i) length f hospital stay (6–8), (ii) frequency of medical and surgical comlications (9, 10) and (iii) surgical interventions (11–13). Moreover it has been demonstrated that MH has an important ole in predicting “sustained clinical remission” induced by biologcal therapy and that, its occurrence, can be considered a positive vent, as it can potentially modify the clinical outcome of IBD, espeially in patients with ulcerative recto-colitis. Many open questions still remain, including: What are the preictive factors of MH? Is the diagnosis of MH simply based on ndoscopic data or does it require histological examination? Which s the contribution of imaging techniques to MH diagnosis? Which s the role of MH in the clinical management of IBD? What is the pecific regional experience of gastroenterologists in MH? In order to attempt to answer some of these key questions dedicated meeting on MH in IBD was organized in September 011 in Trani, Italy; local and nationally recognized expert gasroenterologists, endoscopists, radiologists and pathologists were nvited to submit their personal contribution/opinion focusing on everal controversial key issues. The results of the meeting emphasized the opinion that MH eeds to be validated and requires more prospective studies to conrm the utility of the use of endoscopy, as a frequent and regular iagnostic tool, in evaluating and guiding changes in therapy during ollow-up of IBD patients. Furthermore, the pathologists reinforced he concept that endoscopy with intestinal biopsy represents an mportant tool in the therapeutic decision-making process and in reventing complications. In this issue of Digestive and Liver Disease, we have collected hree review articles as a Mini-Symposium focusing on the current nowledge and the open issues regarding MH in IBD. In the first article entitled “Definition and evaluation of mucosal ealing in clinical practice”, Mazzuoli et al. discuss how a precise efinition of mucosal healing has not yet been established and hat the concept of a “complete absence of all inflammatory